Effect Of Proton Pump Inhibitors Research Articles

Potential Risks Associated With Long-term Use of Proton Pump Inhibitors and the Maintenance Treatment Modality for Patients With Mild Gastroesophageal Reflux Disease.

Gastroesophageal reflux disease (GERD) significantly affects the health-related quality of life and healthcare costs. The prevalence of this disease is increasing in Asia, leading to a rapid increase in the demand of proton pump inhibitors (PPIs). Despite effective symptom management during initial treatment, relapse rates after PPI cessation remain high in patients with GERD, warranting longterm maintenance therapy. Concerns regarding potential side effects related to the long-term use of PPIs are escalating with increased usage. Studies have reported diverse side effects of PPIs, such as increased fracture risk, cardiovascular concerns, enteric infections, neurological diseases, and potential associations with gastric cancer. However, definitive causal relationships remain unclear. This review comprehensively summarizes the latest knowledge on the potential risks associated with long-term use of PPIs. Continuous or noncontinuous therapy can be used as a maintenance treatment modality for GERD. For patients with mild GERD, including those with nonerosive and mildly erosive reflux disease, on-demand therapy following a sufficient period of continuous maintenance therapy is recommended as a long-term maintenance treatment option.

Association between reduced risk of gastrointestinal bleeding related to proton pump inhibitor use and subsequent all-cause death in patients with percutaneous coronary intervention

Abstract Background Gastrointestinal bleeding is the leading cause of post-percutaneous coronary intervention (PCI) bleeding complications which are associated with a high risk for subsequent clinical outcomes. The aim of this study was to estimate association between risk of gastrointestinal bleeding events related to proton pump inhibitor (PPI) use and subsequent clinical outcomes in patients with PCI. Methods The Clinical Deep Data Accumulation System (CLIDAS) is a database for inclusive of patient characteristics, medications, laboratory test, physiological test, cardiac catheterization and PCI treatment, all of which were aggregated from electronic medical records in 7 tertiary hospitals in Japan. Data of 6457 patients who underwent PCI between April 2014 and March 2020 and were then followed for 30 days after the index PCI, were analyzed. These patients were divided into two groups based on use of PPI; the PPI group (n=5285; 82%) and the non-PPI group (n=1172; 18%). Clinical outcomes, defined as gastrointestinal bleeding and all-cause death, were assessed using propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) models. Results Among the 6457 PCI patients, 90 (1.7%) in the PPI group and 31 (2.6%) in the non-PPI group experienced gastrointestinal bleeding events. Adjusting for baseline demographics, comorbidities, and anti-thrombotic treatments, the multivariable Cox hazard model suggested a trend towards a lower risk of gastrointestinal bleeding with PPI use (HR, 0.70; 95%CI, 0.46-1.05; p=0.087). The PSM analysis confirmed a significant association between PPI use and a lower risk of gastrointestinal bleeding (HR, 0.13; 95%CI, 0.04-0.43; p=0.001), consistent with IPTW model results (HR, 0.60; 95%CI, 0.38-0.95; p=0.031). Subgroup analysis showed that PPI use was associated with a low risk of all-cause death in patients with acute coronary syndrome (ACS) (HR, 0.58; 95%CI, 0.36-0.93; p=0.024). Causal mediation analysis indicated an indirect effect of PPI on reducing all-cause death through the suppression of gastrointestinal bleeding events. Conclusion These findings suggested that use of PPI against gastrointestinal bleeding complications might reduce the risk of subsequent all-cause death in ACS patients undergoing PCI.

Knowledge and Attitudes Regarding the Inappropriate Use of Proton Pump Inhibitors Among Students of Umm Al-Qura University in Saudi Arabia: A Cross-Sectional Study.

Background Proton pump inhibitors (PPIs) are commonly prescribed to manage various upper gastrointestinal conditions such as dyspepsia, gastroesophageal reflux disease (GERD), and peptic ulcer disease. However, concerns are increasing regarding their excessive and inappropriate use, particularly in cases where there is no clear medical indication. Inappropriate use can lead to unnecessary side effects and complications, emphasizing the need for better awareness of appropriate PPI use. Objectives This study aimed to assess the knowledge and attitudes of Umm Al-Qura University (UQU) students in Makkah, Saudi Arabia, regarding the inappropriate use of PPIs, highlighting the necessity of targeted educational interventions to improve awareness and promote safe PPI practices. Methods A cross-sectional online survey was conducted among 534 UQU students, aged 18-30, from both health-related and non-health-related majors. Participants were selected through convenience sampling, with the questionnaire distributed via Google Forms across various channels. Data were prepared using Microsoft Excel and analyzed with IBM SPSS Statistics for Windows, V. 25.0 (IBM Corp., Armonk, NY, USA). Results The survey revealed a significant lack of awareness about the potential side effects of PPIs, with 48.1% of participants (n=247) exhibiting low awareness, 30.9% (n=165) demonstrating high awareness, and 21% (n=112) showing moderate understanding. A chi-squared test confirmed that this awareness distribution significantly differed from what was expected, χ²(2, n=534)=60.48, p<0.001. In terms of behavior, 70.4% of participants adhered to good practices regarding PPI use, following appropriate guidelines such as using PPIs only when prescribed, following the correct dosage, and avoiding self-medication. Additionally, 21.3% (n=114) displayed moderate behavior, and 8.2% demonstrated poor behavior by engaging in practices such as using PPIs without medical supervision or not adhering to the recommended dosage and duration. A chi-squared test indicated significant differences in the behavior distribution, χ²(2, n=534)=344.14, p<0.001. Conclusion While most respondents displayed good behavior regarding PPI usage, there remains a significant gap in knowledge and attitudes. Addressing these gaps through targeted educational interventions, such as workshops, e-learning modules, and awareness campaigns, could promote the safe and effective use of PPIs among students in Saudi Arabia. The next steps would involve implementing these programs in collaboration with healthcare professionals and university departments, with effectiveness measured through follow-up surveys, behavior assessments, and analysis of PPI usage trends over time.

Proton Pump Inhibitors Worsen Colorectal Cancer Outcomes in Patients Treated with Bevacizumab

Background: Approximately one-third of patients with advanced colorectal cancer (CRC) and treated with bevacizumab are prescribed proton pump inhibitors (PPIs) or H2 receptor antagonists (H2RAs). However, there is limited data on the effects of PPIs and H2RAs in these patients. To investigate the oncological outcomes of PPI and H2RA use in CRC patients treated with bevacizumab, we performed a retrospective cohort study using the Taiwan National Health Insurance Research Database and Taiwan Cancer Registry Database from 2005 to 2020. Methods: In CRC patients treated with bevacizumab, the PPI users and H2RA users were matched with patients without acid-reducing agents (ARAs) by 1:4 propensity score matching. PPI users and H2RA users were matched with propensity scoring in a 1:1 ratio. We divided patients into 4 cumulative PPI dosage levels to assess the dose–response relationship. The primary endpoints were 5-year overall survival and cancer-specific survival. Results: Compared with ARA non-users, both H2RA users and PPI users were associated with reduced overall survival. PPI users were associated with more significant negative effects on overall survival. Compared with H2RA users, PPI users were associated with lower 5-year overall survival (aHR: 1.19, 95% CI: 1.09–1.31) and cancer-specific survival (aHR: 1.20, 95% CI: 1.09–1.31). A similar dose–response relationship was observed for PPI users in terms of 5-year overall survival and cancer-specific overall survival. Conclusions: Compared to H2AR use, PPI use was associated with dose-dependent poorer oncological outcomes in metastatic CRC patients treated with bevacizumab.

Relationship between proton pump inhibitor prescription and asthma exacerbation among adult patients: a self-controlled case series study.

Proton-pump inhibitors (PPI) are empirically used to treat asthma symptoms such as cough; however, the effectiveness of PPI on asthma exacerbation has not been well studied. We aimed to evaluate the relationship between PPI use and asthma exacerbation using a large administrative claims database in Japan. We conducted a self-controlled case series using the JMDC Claims Database (JMDC, Inc., Tokyo, Japan). The cases included adult patients with asthma who were prescribed PPI and experienced at least one outcome event between January 2015 and December 2019. The primary outcome was the composite outcome of hospital admissions and unscheduled outpatient clinic visits due to asthma exacerbation. We also conducted stratified analyses based on PPI generation, the presence of gastroesophageal reflux disease (GERD), asthma severity, and the number of allergic comorbidities. A total of 7379 eligible patients were included in the study. PPI prescription was associated with a decrease in the composite outcomes (incidence rate ratio, 0.90; 95% confidence interval, 0.87-0.93). However, PPI prescriptions did not affect the outcomes of hospital admissions (incidence rate ratio, 1.34; 95% confidence interval, 0.86-2.10). Stratified analyses based on PPI generation, the presence of GERD, asthma severity (except for severe asthma), and the number of allergic comorbidities yielded consistent results. PPI use was associated with a moderate decrease in asthma exacerbation, regardless of the patient profile. However, this effect was not as strong as the prevention of hospital admissions, and outcome events were not prevented in patients with severe asthma.

The Use of Proton Pump Inhibitors in Patients Aged 65 Years and Above in an Academic Tertiary Referral Hospital

Abstract Background Proton Pump inhibitors (PPIs) are some of the world's most frequently prescribed medications. While PPIs are generally well tolerated, they do carry with them several associated adverse effects ranging from electrolyte disturbances to altering the absorption and thus the effectiveness of other co-administered medications to more severe concerns such as high frequencies of gastrointestinal infections and possibly even respiratory tract infections. Being so commonly prescribed, often for inappropriate or unknown indications, they become an important and relatively easy target for review. Methods A retrospective review of electronic health care records of individuals aged 65 years and older admitted under general medical teams in an academic tertiary referral hospital over the course of a calendar month was undertaken to evaluate typical PPI usage encountered, including frequency of PPI prescriptions at both admission and discharge, recorded indications, and impact of review by clinical pharmacists. Results Of the 77 individuals included in this study, 59 (77%) were prescribed a PPI at some point during admission. Of the patients surviving to discharge, 98% (n = 53) remained on a PPI at discharge. One patient (2%) had a PPI stopped before discharge. Indications for a PPI were explicitly stated in 25% (n = 15) of patients prescribed a PPI. A further 27% (n = 16) could have an indication derived from information within the electronic health record. One (2%) patient was prescribed a PPI, and a duration was indicated. Conclusion Most PPI prescriptions lack documentation regarding the indication and intended duration and may be inappropriately prescribed. The frequency of usage of PPIs in an older population that is more at risk of the adverse effects of PPIs makes them ideal targets and models for evaluation of prescribing practices and deprescribing efforts.

Longitudinal Microbiome Changes in Children Exposed to Proton Pump Inhibitors.

Proton pump inhibitor (PPI) use has been associated with an increased risk of gastrointestinal and upper respiratory infections in children. There are limited longitudinal data on the effect of PPI in children. The goal of this prospective observational study was to compare the stool and oropharyngeal microbiome of children before and after starting PPIs. We prospectively recruited participants from a gastroenterology clinic. Consented participants provided stool samples and oropharyngeal swabs at baseline and after 8 weeks of PPI therapy. Microbiome changes were measured by analyzing 16S sequencing from both body sites at both time points. Thirty-four participants completed the study and provided samples both at baseline and after 8 weeks on PPI therapy. Of those, 24 participants had sufficient sequencing from both stool and oropharyngeal samples at both time points. There were no differences between the pre-PPI and post-PPI samples using beta-diversity metrics in either the oropharynx or stool. There were, however, significant changes in specific taxa. There was an enrichment of Streptococcus in the stool after PPI use and a reduction in the relative abundance of Bifidobacterium , Peptostreptococcus , and Turicibacter ( P -values < 0.01). Furthermore, there was an increase in the relative abundance of oropharyngeal bacteria in the stool after PPI therapy. This enrichment of oropharyngeal bacteria in the stool was most prominent in younger participants. Further investigation is needed to determine the clinical and microbial factors that predispose or protect against microbiome changes due to PPI use and why young children are more susceptible to this PPI effect.

A network meta-analysis: evaluating the efficacy and safety of concurrent proton pump inhibitors and clopidogrel therapy in post-PCI patients.

The objective of this research was to evaluate the risk of major adverse cardiovascular events (MACEs) associated with the use of various proton pump inhibitors (PPIs) in combination with clopidogrel in patients who underwent percutaneous coronary intervention (PCI). To accomplish this, we analyzed data from randomized controlled trials and retrospective cohort studies sourced from key electronic databases. These studies specifically examined the effects of different PPIs, such as lansoprazole, esomeprazole, omeprazole, rabeprazole, and pantoprazole, when used in conjunction with clopidogrel on MACEs. The primary focus was on the differential impact of these PPIs, while the secondary focus was on the comparison of gastrointestinal (GI) bleeding events in groups receiving different PPIs with clopidogrel vs. a placebo group. This study's protocol was officially registered with INPLASY (INPLASY2024-2-0009). We conducted a network meta-analysis involving 16 studies with a total of 145,999 patients. Our findings indicated that rabeprazole when combined with clopidogrel, had the lowest increase in MACE risk (effect size, 1.05, 95% CI: 0.66-1.66), while lansoprazole was associated with the highest risk increase (effect size, 1.48, 95% CI: 1.22-1.80). Esomeprazole (effect size, 1.28, 95% CI: 1.09-1.51), omeprazole (effect size, 1.23, 95% CI: 1.07-1.43), and pantoprazole (effect size, 1.38, 95% CI: 1.18-1.60) also significantly increased MACE risk. For the secondary outcome, esomeprazole (effect size, 0.30, 95% CI: 0.09-0.94), omeprazole (effect size, 0.34, 95% CI: 0.14-0.81), and pantoprazole (effect size, 0.33, 95% CI: 0.13-0.84) demonstrated an increased potential for GI bleeding prevention. In conclusion, the combination of lansoprazole and clopidogrel was found to significantly elevate the risk of MACEs without offering GI protection in post-PCI patients. This study is the first network meta-analysis to identify the most effective regimen for the concurrent use of clopidogrel with individual PPIs. https://inplasy.com/inplasy-2024-2-0009/, identifier (INPLASY2024-2-0009).

Salivary pepsin testing for laryngopharyngeal reflux: will it change our management?

This review focus on the clinical value of salivary and laryngopharyngeal tissue pepsin measurement in the diagnosis and treatment of laryngopharyngeal reflux (LPR). A growing body of research suggests that salivary pepsin detection provides a noninvasive method for the identifying LPR occurrence. Pepsin detection testing is still variable, and an optimal method that balances utility with accuracy has not been agreed. Timing and number of test samples recommended also remains controversial, however literature indicates that increasing the number of tests over a day increases pepsin detection rate. It remains unclear whether detection of pepsin alone can be used to confirm LPR diagnosis. Pepsin positivity is correlated with improved response to proton pump inhibitor (PPI) therapy, and therefore may play a role in guiding therapeutic choices. Detection of pepsin in laryngeal tissue has the same clinical value as detection in saliva and requires further investigation to determine utility. As a noninvasive method for the diagnosis of LPR, the detection of salivary pepsin in the oropharynx shows potential clinical value, however the exact method of detection and diagnostic values are unclear. Salivary or tissue-based pepsin detection may be helpful in predicting therapeutic effects of PPI and providing personalized treatment options. The detection threshold of salivary pepsin may be different in different countries and regions. Timing and number of samples needed for detection is still controversial.

Overutilization of Proton Pump Inhibitors (PPIs) in a Community-Based Hospital: A QI Initiative

Introduction: Proton pump inhibitors (PPIs) are indicated for GERD, erosive esophagitis, and prophylactic use in patients at high risk for stress ulcerations. Long-term PPI therapy is associated with increased incidence of C. diff infections and community- and hospital-acquired pneumonia. Discontinuation of stress ulcer prophylaxis upon discharge and reevaluation of continued therapy will help reduce chronic, inappropriate treatment, which predisposes patients to adverse side effects. Aim: We sought to reform the process of inpatient PPI prescriptions based on clinical indications of therapy in order to reduce use and associated costs of PPIs by 30% over 6 months. Model for Improvement: We obtained an IRB exemption for a retrospective chart review study and collected pre-intervention data from 200 patients who had received PPI therapy between July-Aug 2022. Of these, 186 met inclusion criteria. We identified PPT overuse among all inpatient admissions, including those admitted under teaching services. Evaluating the timing of PPI initiation after admission, we found that a majority (83.8%) were started upon admission; 28.5% required PPIs throughout; and 25.2% of orders were placed within 1 day of discharge. The average duration of therapy was 3.9  2.59 days. On average, 50.5% of patients had a prior diagnosis of GERD, gastritis, or erosive esophagitis, justifying initiation of PPI therapy. However, almost a third (32.8%) met the criteria for stress ulcer prophylaxis. 17% of the cohort developed an adverse side effect, and almost 53% of patients were discharged with a new prescription for PPI. Measures: Root cause analysis revealed a lack of knowledge regarding adverse PPI effects leading to longer hospital stays. During the first PDSA, we conducted a session on “Use of PPI Inhibitors: Indications for Inpatient Prescriptions and Stress Ulcer Prophylaxis” in April 2023, educating Internal Medicine and Family Medicine resident teaching services about PPI therapy indications, contraindications, and adverse effects. Results: After our educational intervention, we collected and analyzed data from May 2023 to August 2023 and found 301 patients who met inclusion criteria. Their average age was 73.29 years. 169 patients (56%) had pre-existing diagnoses (GERD or erosive esophagitis), justifying initiation of Protonix. Of the remaining 132 without pre-existing conditions, 44 (35%) met criteria for starting stress ulcer prophylaxis. This was a 3% increase in appropriate utilization when compared to our pre-intervention data. 181 patients were discharged with a prescription for pantoprazole, of which 46 were PPI-naïve prior to admission. Conclusion: We found a decrease in inappropriate inpatient PPI administration by 3% after education. Although the post-intervention sample size was larger, the education resulted in a positive response in 1 month. The next PDSA cycle will alter the EMR order to provide only 3 orders for pantoprazole – one oral, one IV, and one for infusion, and orders will also require the selection of indication.

Proton Pump Inhibitors and Risk of COVID-19 Infection in Children

To evaluate the influence of proton pump inhibitor (PPI) use on COVID-19 susceptibility and severity in children. This retrospective, case-control study included all children ≤21years undergoing COVID-19 polymerase chain reaction testing at a tertiary children's hospital between March 2020 and January 2023. The main exposure was PPI usage. The primary outcome was COVID-19 infection. The secondary outcome was COVID-19 hospitalization. Log-binomial regressions were used to examine associations between PPI use and these outcomes. 116 209 patients age 8.5±6.2years underwent 234 867 COVID-19 tests. Current PPI use was associated with a decreased risk of COVID-19 test positivity compared with PPI nonuse [RR 0.85 (95% CI 0.76, 0.94), P=.002]; however, there was a significant interaction with time of testing, and an effect of PPIs was no longer seen in the final months of the study following lessening of COVID-19 precautions [RR 1.04 (95% CI 0.0.80, 1.36), P=.77]. PPI use was not associated with risk of hospitalization in patients positive for COVID-19 after adjusting for other hospitalization risk factors [RR 0.85 (95% CI 0.64, 1.13), P=.26]. We did not find an association between PPI use and increased COVID-19 susceptibility or severity in this pediatric sample. These results provide reassuring evidence that PPIs may not worsen COVID-19 outcomes in children.

Elderly Care: Commonly Prescribed Gastrointestinal Drugs Associate With Cognitive Decline

Background — Gastrointestinal (GI) medications are among the most common drugs used in old age. Recent studies reported heterogeneous association between proton pump inhibitors (PPIs) with neurological complications such as memory impairment. Objective — This research was conducted to assess the effect of different categories of GI drugs on cognitive function of older adults. Methods — This case-control study was carried-out on adults 60 or more years of age and over living in Amirkola, northern Iran, where health-related data were available in the database of the second phase of the Amirkola Health and Ageing Cohort Project (AHAP). Cognitive function of the elderly was examined with the Mini-Mental State Examination (MMSE) screening test. Results — Among 900 examined individuals, total intake of GI medications exhibited no significant effect on cognitive function of older adults [adjusted OR:1.049 (95% CI: 0.757-1.452); p=0.775]; however, a statistically significant effects of PPIs [adjusted OR=1.571 (1.001-2.467); p=0.050) and medicinal drugs affecting GI tract movements [adjusted OR=2.202 (1.180-4.111); p=0.013) on cognitive function were observed. Conclusion — Although total intake of GI medications did not cause a statistically significant impact on cognitive function of older adults, PPIs and medicinal drugs affecting GI tract movements had a significant effect.

Effect of proton pump inhibitors compared to histamine-2 receptor antagonists on bleeding management and wound healing after endoscopic mucosal resection or endoscopic submucosal dissection: A meta-analysis of randomized clinical trials.

Proton pump inhibitors (PPIs) and histamine type-2 receptor antagonists (H2RAs) are generally effective in preventing delayed bleeding and healing artificial wounds after endoscopic mucosal resection (EMR) or endoscopic submucosal dissection (ESD). This study aimed to review the therapeutic effects of PPIs and H2RAs on damage caused by EMR and ESD. Thirteen articles were collected between 2002 and 2022 by searching Medlib, ScienceDirect, PubMed, International Scientific Indexing (ISI), Embase, and Scopus databases using valid keywords. The main inclusion criteria were delayed wound healing, bleeding, epigastric pain, intraoperative bleeding, and perforation. The odds ratio (OR) and 95% confidence interval (95% CI) were evaluated using a random or fixed effects model. Data analysis was performed using Stata v. 14.2. A total of 13 articles including 1,483 patients were analyzed. The results showed that delayed bleeding was significantly less frequent in the PPI group than in the H2RA group (OR = 0.6; 95% CI: 0.39-0.92). Subgroup analysis showed that PPI was more effective in preventing delayed bleeding than H2RA for ESD wounds (OR = 0.65; 95% CI: 0.44-1.08). There was no statistically significant difference between both groups regarding the incidence of epigastric pain, intraoperative bleeding, wound healing, and perforation after endoscopic treatments. The meta-analysis results reveal that PPI is more effective than H2RA in preventing delayed bleeding after endoscopic treatment, particularly in patients treated with ESD. However, there was no significant difference between PPI and H2RA in terms of intraoperative bleeding, epigastric pain, wound healing, and perforation from endoscopic therapy.

Proton Pump Inhibitor for Gastrointestinal Bleeding in Patients with Myocardial Infarction on Dual-Antiplatelet Therapy: A Nationwide Cohort Study.

Guidelines provide various recommendations for the use of proton pump inhibitors (PPI) to prevent upper gastrointestinal (UGI) bleeding in acute myocardial infarction (MI) treatment with dual antiplatelet therapy (DAPT). We evaluated the effects of PPIs in reducing the risk of severe UGI bleeding in patients with MI receiving DAPT. This retrospective cohort study included patients admitted for acute MI between 2014 and 2018, based on a nationwide health claims database in Korea. Primary outcome was admission for severe UGI bleeding requiring transfusion within 1 year of MI diagnosis. A multivariable Cox regression model was used to calculate the association between PPI use and severe UGI bleeding risk. Of 100,556 patients with MI on DAPT (mean age, 63.7 years; 75.4% men), 37% were prescribed PPIs. Based on risk assessment for UGI bleeding, among 6,392 (6.4%) high-risk and 94,164 (93.6%) low-risk patients, 50.5% and 35.8% received PPIs, respectively. Overall, 0.5% of the patients experienced severe UGI bleeding within 1 year after MI. The use of PPI was associated with a reduced risk of severe UGI bleeding (hazard ratio [HR], 0.57; 95% confidence interval [CI], 0.47-0.70; P < 0.001). The benefits of PPIs were consistent in high-risk (HR, 0.71; 95% CI, 0.45-1.13; P = 0.147) and low-risk (HR, 0.54; 95% CI, 0.43-0.68; P < 0.001) patients (P for interaction = 0.481). Among Korean patients with MI receiving DAPT, PPIs were underutilized, even among those at high risk of severe UGI bleeding. Nonetheless, PPI use reduced severe UGI bleeding in low- and high-risk groups.

Effects of proton pump inhibitors on inflammatory bowel disease: An updated review.

Inflammatory bowel disease (IBD) is believed to be caused by various factors, including abnormalities in disease susceptibility genes, environmental factors, immune factors, and intestinal bacteria. Proton pump inhibitors (PPIs) are the primary drugs used to treat acid-related diseases. They are also commonly prescribed to patients with IBD. Recent studies have suggested a potential association between the use of certain medications, such as PPIs, and the occurrence and progression of IBD. In this review, we summarize the potential impact of PPIs on IBD and analyze the underlying mechanisms. Our findings may provide insights for conducting further investigations into the effects of PPIs on IBD and serve as an important reminder for physicians to exercise caution when prescribing PPIs to patients with IBD.

Changes in the Gastrointestinal Microbiota Induced by Proton Pump Inhibitors-A Review of Findings from Experimental Trials.

The use of proton pump inhibitors (PPIs) has increased considerably in many Western countries, and there is concern that numerous conditions and diseases associated with PPI use may be adverse events. The main function of gastric acid is to defend the organism against orally ingested microorganisms, and there is also concern that alterations not only in the gastric microbiome but also the downstream intestinal microbiome may increase the risk of disease or alter the course of preexisting disease. The current study is a systematic review of the available evidence from experimental trials investigating the effects of PPIs on the gastrointestinal microbiota by next-generation sequencing. Thirteen studies were identified. The effects of PPIs were seen on alterations in diversity and richness in some of the studies, while a larger proportion of the studies detected alterations at various taxonomic levels. The general finding was that PPI use caused an increase in bacteria normally found in the oral microbiota in both the upper and lower GI tract. The most consistent taxonomic alterations seemed to be increases in oral flora along the axis Streptococcaceae and Streptococcus at genus level and various Streptococcus spp., as well as Veillonellaceae, Veillonella and Haemophilus.

Awareness of Proton Pump Inhibitor Adverse Events and Treatment Pattern Change According to Physician Practice: A National Questionnaire Study in Korea.

Although adverse events of proton pump inhibitors (PPIs) have been reported, there are few studies on physicians' perceptions. We aimed to investigate physicians' awareness of PPI-related adverse events and changes in treatment patterns according to their practice. We conducted an online survey of physicians using a 15-item questionnaire. The survey queried respondents' demographic information, PPI prescription patterns, perceptions, and concerns on the reported PPI-related adverse events. Concerns regarding the adverse events of PPI were assessed by dividing them into possibilities and medical causality. Of the 450 respondents, 430 were specialists, and 232 were gastroenterologists. A total of 87.8% of the respondents were generally or well aware of the adverse effects of PPI, 29.1% considered side effects when prescribing PPI, and 14.6% explained them to patients. Specialists were more aware of the side effects of PPI than general practitioners (p = 0.005), and gastroenterologists were more aware of the side effects of PPI than non-gastroenterologists (p < 0.001). However, gastroenterologists explained less to patients (p = 0.001) and preferred to reduce the dose of PPI rather than discontinue it. The adverse events that were recognized as having the highest probability of occurrence and strongest association with PPI use were bone diseases, Clostridium difficile infection, gastrointestinal infection, pneumonia, and interactions with anti-thrombotic drugs. Physicians' awareness of PPI-related adverse events and treatment patterns differed significantly according to their positions and practice. Although a number of adverse events of PPIs were reported, physicians seem to accept their significance differently according to their specialty and practice patterns.

Adverse Effects of Long-term Proton Pump Inhibitors in Chronic Liver Disease Patients – A Preliminary Article Review

Background: Proton pump inhibitors (PPIs) are widely prescribed medications for the management of gastroesophageal reflux disease (GERD) and peptic ulcer disease. Despite their efficacy, concerns have emerged regarding their potential adverse effects, particularly in patients with chronic liver disease (CLD). CLD patients often experience gastrointestinal symptoms and may be prescribed PPIs, but the impact of PPI use on liver function and disease progression remains uncertain. Scope: This study aims to evaluate the adverse effects of PPIs on CLD patients through a review of available literature. The scope encompasses a review of studies examining the association between PPI use and liver-related outcomes, including hepatic encephalopathy, hepatic decompensation, liver cirrhosis progression, and mortality, among CLD patients. Method: A scoping review of relevant literature were conducted to identify studies investigating the adverse effects of PPIs in CLD patients. Databases including PubMed and Google Scholar were searched for articles published up to January, 1 2023. Eligible studies were selected based on predefined inclusion criteria. Results: The review identified 27 studies meeting the inclusion criteria, comprising observational studies and meta-analysis. The review revealed a significant association between PPI use and adverse liver outcomes in CLD patients. Specifically, PPI use was associated with increased risk of SBP based on studies reviewed, while other complications remained inconclusive. Conclusion: The findings suggest that PPI use may have detrimental effects on disease progression in CLD patients, Long-term use of PPIs can lead to higher risk of SBP in CLD patients. Clinicians should exercise caution when prescribing PPIs to this vulnerable population and consider alternative treatment options or minimize PPI use to mitigate potential adverse outcomes. Further research is warranted to elucidate the underlying mechanisms, confirm the effect of PPIs toward other complications of CLD and establish guidelines for PPI use in CLD patients.

The effect of rabeprazole on the secretory and motor function of the gastrointestinal tract

Parietal cell proton pump inhibitors (PPIs) have become firmly established in clinician practice. When discussing the features of their action, as a rule, researchers focus on their antisecretory effect. In the available literature, we found only a single report on the effect of PPIs on the motor-evacuation function of the gastrointestinal tract (GIT). We have found that the PPI rabeprazole not only has an antisecretory effect, but also normalizes the motor-evacuation function of all parts of the gastrointestinal tract. In this regard, it can be used in patients with gastric hypersecretion in functional gastrointestinal disorders (FGID) with impaired motor-evacuation function. Aim. To study the effect of the antisecretory drug rabeprazole on the state of gastrointestinal motility in patients suffering from FGID of the gastrointestinal tract and overlap syndrome (overlap syndrome) with functional dyspepsia (FD) with gastric hypersecretion and irritable bowel syndrome (IBS). Material and methods. We examined 30 patients suffering from FGID of the gastrointestinal tract and cross syndrome - FD with gastric hypersecretion and IBS. To relieve clinical symptoms of FD, the drug rabeprazole 20 mg was prescribed once a day for 14 days. Before and after the start of treatment, patients were examined with VAS and SF-36 tests, intragastric pH-metry and peripheral electrogastroenterocolography (EGECG) were performed. Results. In all 30 patients with FGID of the gastrointestinal tract with FD and overlap syndrome with IBS, gastric hypersecretion was eliminated within 3 hours after taking 20 mg of rabeprazole. 2 weeks after the start of treatment, abdominal pain and heartburn were completely eliminated in 28 (93.3%) patients. In all (100%) patients with FGID of the gastrointestinal tract with gastric hypersecretion and overlap syndrome, after two weeks of treatment, sour belching disappeared, and nausea disappeared in 23 (77%) patients. Rabeprazole therapy in the examined individuals was accompanied by a marked improvement in the quality of life in all assessed SF-36 parameters. 2 weeks after starting rabeprazole, in patients with FGID of the gastrointestinal tract and overlap syndrome of FD and IBS, the frequency of bowel movements and stool quality were normalized, and according to the results of EGECG, the relative myoelectric activity (P(i)/PS) of the gastrointestinal tract and the rhythmicity coefficient (Kritm) were normalized. Conclusion. Rabeprazole quickly neutralizes gastric secretion and helps eliminate symptoms of FD. It also has a beneficial effect on the motor-evacuation function of all parts of the gastrointestinal tract, normalizing the frequency of bowel movements, stool quality and myoelectric activity of all parts of the gastrointestinal tract according to EGECG. Rabeprazole can be used in patients with FGID with FD with gastric hypersecretion and overlap syndrome with IBS.

Proton pump inhibitors, bone and phosphocalcic metabolism

Proton pump inhibitors (PPIs) are widely used for acid-related gastrointestinal disorders; however, concerns have arisen about their prolonged and inappropriate use. Although generally considered safe, recent evidence has linked PPI use with an increased risk of kidney disease, stomach cancer, pneumonia, dementia, cardiovascular events and potential bone health problems. This systematic review examines the effects of PPIs on bone health, including osteoporosis and changes in phosphocalcic and magnesium metabolism, through a comprehensive analysis of the recent literature. The relationship between PPIs, bone mineral density and fracture risk, especially in populations with comorbidities, is complex and we propose a focus based on recent data. Studies of the effect of PPI use on bone mineral density have shown mixed results and require further investigation. Observational studies have indicated an increased risk of fractures, particularly vertebral fractures, associated with PPI use. Recent meta-analyses have confirmed an association between PPI use and hip fractures with a dose-dependent effect. More recently, PPIs have been associated with serious disturbances in phosphocalcic and magnesium metabolism that require careful management and discontinuation. Proton pump inhibitor-induced hypomagnesemia (PPIH) is a well-established phenomenon. In addition, hypocalcemia secondary to severe hypomagnesemia has been described. Despite growing evidence of PPI-related risks, further research is essential to better understand the complex mechanisms, as most data are from observational studies and do not establish a causal relationship. This review emphasizes the need for judicious prescription practices, particularly in long-term use scenarios and rheumatological contexts.